MiR-130a activates the VEGFR2/STAT3/HIF1? axis to potentiate the vasoregenerative capacity of endothelial colony-forming cells in hypoxia.

ABSTRACT: Hypoxia modulates reparative angiogenesis, which is a tightly regulated pathophysiological process. MicroRNAs (miRNAs) are important regulators of gene expression in hypoxia and angiogenesis. However, we do not yet have a clear understanding of how hypoxia-induced miRNAs fine-tune vasoreparative processes. Here, we identify miR-130a as a mediator of the hypoxic response in human primary endothelial colony-forming cells (ECFCs), a well-characterized subtype of endothelial progenitors. Under hypoxic conditions of 1% O₂, miR-130a gain-of-function enhances ECFC pro-angiogenic capacity in vitro and potentiates their vasoreparative properties in vivo. Mechanistically, miR-130a orchestrates upregulation of VEGFR2, activation of STAT3, and accumulation of HIF1? via translational inhibition of Ddx6. These findings unveil a new role for miR-130a in hypoxia, whereby it activates the VEGFR2/STAT3/HIF1? axis to enhance the vasoregenerative capacity of ECFCs.

SUBMITTER: Guduric-Fuchs J 

PROVIDER: S-EPMC7869000 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature